title: Administration of IL-4 prevents autoimmune diabetes but enhances pancreatic insulitis in NOD mice.
abstract: The present study demonstrated that the administration of recombinant interleukin-4 (rIL-4) prevented overt diabetes in nonobese diabetic (NOD) mice whose T cells produced relatively low amounts of IL-4. However, massive insulitis was observed in rIL-4-treated NOD mice. The flow cytometric analysis of islet-infiltrating T cells revealed that the number of CD45RBlowCD4+ T cells was significantly increased by in vivo administration of rIL-4. By measuring the cytokine production of splenic T cells after stimulation, it was shown that CD45RBlowCD4+ T cells predominantly produced IL-4 and IL-10 but produced less IL-2 and interferon-gamma (IFN-gamma). A semiquantitative reverse-transcriptase polymerase chain reaction assay revealed a higher expression of IL-4 and IL-10 mRNA and an apparent decrease in IFN-gamma mRNA in the islets of NOD mice which were administered rIL-4. These results suggested that autoreactive CD45RBlowCD4+ T helper 2 (Th2)-like cells which developed following rIL-4 administration were predominant in the infiltrate of the islets, and overt diabetes was prevented. On the other hand, when splenocytes from rIL-4-treated NOD mice were transferred to irradiated NOD recipients, along with splenocytes from diabetic NOD mice, all of the recipient mice became diabetic within 8 weeks after transfer. Considered together, a supplement of rIL-4 administered to NOD mice may protect against autoimmune diabetes by facilitating the development of Th2-like autoreactive T cells in the islets.
authors.affiliation: Second Department of Internal Medicine, Department of Geriatric Medicine, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tominaga
authors.forename: M
authors.initials: M
authors.lastname: Nagata
authors.forename: H
authors.initials: H
authors.lastname: Yasuda
authors.forename: N
authors.initials: N
authors.lastname: Okamoto
authors.forename: K
authors.initials: K
authors.lastname: Arisawa
authors.forename: H
authors.initials: H
authors.lastname: Moriyama
authors.forename: M
authors.initials: M
authors.lastname: Miki
authors.forename: K
authors.initials: K
authors.lastname: Yokono
authors.forename: M
authors.initials: M
authors.lastname: Kasuga
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000008:administration & dosage / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016753:Interleukin-10; D015847:Interleukin-4; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1